Faculty Bibliography

INTRODUCTION/BACKGROUND:Accurate preoperative evaluation of pancreatic cysts is essential. However, cytology and biochemical analysis are often limited by low cellularity, and risk stratification is critical for management. PancreaSeq Genomic Classifier (GC) analyzes cyst fluid for molecular alterations to aid diagnosis and risk assessment. MATERIALS AND METHODS/METHODS:We retrospectively analyzed 219 pancreatic cysts from 206 patients using PancreaSeq GC, integrating molecular findings with cytology, biochemical, imaging, surgical pathology, and follow-up. RESULTS:PancreaSeq GC successfully analyzed 216/219 cysts (99%) and detected alterations in 182 (83%). Among cases with both cytology and molecular data (n = 201), concordance was high in cytologically mucinous neoplasms (94%) and atypical cases (95%). Notably, among cases reported as negative for malignancy or nondiagnostic on cytology (n = 128), PancreaSeq GC identified mucinous neoplasms in 82 cases (64%), demonstrating added value in limited samples. Surgical pathology correlation (n = 24) showed excellent performance for distinguishing mucinous from nonmucinous cysts (area under the curve [AUC] = 0.94, P < 0.001). Risk stratification for detection of any dysplasia yielded an AUC of 0.78 (P = 0.006), and for high-grade dysplasia an AUC of 0.74 (P = 0.046). PancreaSeq GC reliably predicted neuroendocrine tumors, but the sensitivity for focal high-grade dysplasia in mucinous neoplasms and serous cystadenoma was limited. Compared with carcinoembryonic antigen (CEA), cyst fluid glucose showed higher sensitivity but lower specificity for mucinous cyst detection. CONCLUSIONS:PancreaSeq GC provides significant diagnostic and risk-stratification value that complements cytological evaluation, particularly in indeterminate or nondiagnostic cytology specimens and when biochemical data are unavailable. Integration of molecular findings improves cyst classification and dysplasia risk assessment. Multidisciplinary assessment remains essential, given the assay's limited sensitivity for focal high-grade dysplasia and serous cystadenomas.

This study presents two cases of lipid-rich pancreatic neuroendocrine tumors (PanNETs), a rare variant posing significant diagnostic challenges in fine needle aspiration (FNA) cytology and small biopsies. The first case involves an elderly male with a pancreatic tumor, displaying distinct cytoplasmic vacuoles, while the second case is a middle-aged male present with a pancreatic tail mass exhibiting foamy cytoplasm and eccentric nuclei, infiltrating in the stroma. Both cases did not exhibit typical morphologic features of PanNET but demonstrated cytomorphologic features and infiltrative growth patterns that mimicked adenocarcinoma. Further work-up demonstrated that both tumors were immunoreactive for synaptophysin and chromogranin, and were interpreted as well-differentiated, PanNET, lipid-rich variant. The study highlights the overlapping morphological features between lipid-rich PanNETs and other pancreatic neoplasms and underscores the importance of comprehensive cytological and immunohistochemical analysis for accurately diagnosing this variant, particularly due to the risk of misinterpreting it as pancreatic adenocarcinoma. Recognizing lipid-rich PanNETs is crucial for appropriate clinical management, as their identification can significantly impact treatment decisions and patient outcomes.

OBJECTIVES/OBJECTIVE:The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months. METHODS:Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results. RESULTS:There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%. CONCLUSIONS:A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.

Introduction: The utility of The Paris System (TPS) in diagnosing low-grade urothelial neoplasm (LGUN) on urine cytology is controversial due to the strict requirement for fibrovascular cores, and low sensitivity/specificity. Many LGUNs are classified as atypical urothelial cells (AUC) on cytology, which compromises the performance and utility of TPS. Here, we studied cytomorphologic features of LGUN in urine samples to determine which features were commonly observed.
Material(s) and Method(s): Twenty-two urine cytology cases with corresponding (within 2 months) LGUN histologic diagnosis were retrieved for this pilot study and were evaluated by one cytopathologist for the presence of clusters, cercariform cells, hyperchromasia, irregular nuclear rim, papillary architecture +/-fibrovascular core, and nucleus:cytoplasm (N:C) ratio (Figure 1). Hierarchical cluster analysis (Ward's Method) was used to classify the features.
Result(s): Of the 22 urines, one was voided (4.5%) and 21 were instrumented (95.5%). Majority (77.3%) were diagnosed as AUC, 1 was suspicious for urothelial carcinoma (4.5%), 4 cases were graded as LGUN (18.2%, Table 1). Clustering analysis demonstrated that the morphologic features abundantly present in the urine specimen of LGUN included: clusters (77.3%), N:C ratio >50% (85.4%), and papillary architecture without a core (72.7%). The features that were mostly absent in LGUN specimens included: irregular nuclear rim (0%), papillary formation with a core (0%), hyperchromasia (9.1%), coarse chromatin (22.7%), and cercariform cells (36.3%). (Table 2).
Conclusion(s): Papillary formation with a fibrovascular core, the most convincing feature of LGUN, was not present in our pilot cohort of LGUN urines. However, our study describes additional cytomorphologic features that may be useful in identifying LGUN in urine cytology. Our research will continue with the evaluation of a larger cohort of LGUN cases with corresponding urine cytology in order to further investigate these findings